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Recent studies on the amyloidogenesis of SARS\u2010CoV\u20102 protein segments have raised concerns on their potential link to post\u2010infection neurodegeneration, however, the mechanisms remain unclear. Herein, we investigated the structure, stability, and amyloidogenic propensity of a nine\u2010residue segment (SK9) of the SARS\u2010CoV\u20102 envelope protein and their impact on neuronal protein \u03b1\u2010synuclein (\u03b1Syn) aggregation. Specifically, the amino acid sequence of the SK9 wildtype has been modified from a basic and positively charged peptide (SFYVYSRVK), to a nearly neutral and more hydrophobic peptide (SAAVASAVK, labelled as SK9 var1), and to an acidic and negatively charged peptide (SDAVANAVK, labelled as SK9 var2). Our findings reveal that the SK9 wildtype exhibited a pronounced amyloidogenic propensity due to its disordered and unstable nature, while the SK9 variants possessed more ordered and stable structures preventing the amyloid formation. Significantly, the SK9 wildtype demonstrated distinct effect on \u03b1Syn aggregation kinetics and aggregate morphology to facilitate the formation of \u03b1Syn aggregates with enhanced resistance against enzymatic degradation. This study highlights the potential of modifying short peptide sequences to fine\u2010tune their properties, providing insights into understanding and regulating viral\u2010induced amyloid aggregations.<\/jats:p>","DOI":"10.1002\/cbic.202400598","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T12:09:57Z","timestamp":1730376597000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Distinct Effects of SARS\u2010CoV\u20102 Protein Segments on Structural Stability, Amyloidogenic Potential, and \u03b1\u2010Synuclein Aggregation"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6206-8014","authenticated-orcid":false,"given":"Vince","family":"St. Dollente Mesias","sequence":"first","affiliation":[{"name":"Department of Chemistry, The Hong Kong University of Science and Technology  Clearwater Bay Road, Kowloon Hong Kong SAR 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